The main objectives continue to be the study of the metabolism of the narcotic antagonists, naloxone and naltrexone. Since identification of the 6 alpha and 68 metabolites of both naloxone and naltrexone have been accomplished and the narcotic antagonist activities of these metabolites have been shown to possess different activities, a thorough study of the enzyme systems will be made. Thus far, the enzymes for carrying out the reduction has been found to be different between the chicken and the rabbit (which probably is analogous to that in man) and thus, the enzyme for production of the 6 alpha metabolites appears to be different from that for the 6 beta metabolites. Because we now know that there are animals which produce both metabolites, the phylogenetic study of the enzymes in these various species will be continued. BIBLIOGRAPHIC REFERENCES: J. M. Fujimoto, S. Roerig, R.I.H. Wang, N. Chatterjie, C.E. Inturrisi. Narcotic antagonist activity of several metabolites of naloxone and naltrexone tested in morphine dependent mice. Proc. Soc. Exp. Biol. Med. 148: 443-448, 1975. J. M. Fujimoto, D.L. Roerig and R.I.H. Wang. Macroreticular polystyrene in pharmacological procedures. Ind. Eng. Chem., Prod. Res. Dev. 14:90, 1975.